Compound 6-chloro-3-[2-(1-ethyl-propylamino)-3,4-dioxo-cyclobut-1-enylamino]-2-hydroxy-N-methoxy-N-methyl-benzenesulfonamide and a method of preparing same have been disclosed in international patent application WO 2010/015613 as Example 8. Compound 6-chloro-3-[2-(1-ethyl-propylamino)-3,4-dioxo-cyclobut-1-enylamino]-2-hydroxy-N-methoxy-N-methyl-benzenesulfonamide is a pharmaceutically active agent and acts as a CXCR2 receptor antagonist and is useful in the treatment of inflammatory, obstructive or allergic conditions and diseases, for example for the treatment of chronic obstructive pulmonary disease (COPD).
Oral delivery of pharmaceutically active agents is generally the delivery route of choice, even when treating respiratory diseases, since it is convenient, relatively easy and generally painless resulting in greater patient compliance relative to other modes of delivery. However, biological, chemical and physical barriers such as poor solubility, varying pH in the gastrointestinal tract, powerful digestive enzymes and impermeable gastrointestinal membranes make oral delivery of some pharmaceutically active agents to mammals problematic or even impossible.
Compound 6-chloro-3-[2-(1-ethyl-propylamino)-3,4-dioxo-cyclobut-1-enylamino]-2-hydroxy-N-methoxy-N-methyl-benzenesulfonamide of formula I
is a weakly acidic compound and is practically insoluble in aqueous solution at pH 1.0-7.0 as a free acid (<0.005 mg/ml).
Accordingly, there is a need to provide novel forms of 6-chloro-3-[2-(1-ethyl-propylamino)-3,4-dioxo-cyclobut-1-enylamino]-2-hydroxy-N-methoxy-N-methyl-benzenesulfonamide which show at least some superior characteristics over the free acid form. There is also a need for formulations which provide effective bioavailability of 6-chloro-3-[2-(1-ethyl-propylamino)-3,4-dioxo-cyclobut-1-enylamino]-2-hydroxy-N-methoxy-N-methyl-benzenesulfonamide in plasma.
The present invention provides such a novel salt form of 6-chloro-3-[2-(1-ethyl-propylamino)-3,4-dioxo-cyclobut-1-enylamino]-2-hydroxy-N-methoxy-N-methyl-benzenesulfonamide and formulation of same which solve the above problems or at least provide a useful alternative to the known salts and formulations of this compound.